Electrophysiological information is obtained by direct recordings from electrodes placed in the temporal lobe by means of stereotactic coordinates in young patients suffering from certain forms of epilepsy. When electrical abnormality is determined to lie in one temporal lobe, that lobe is resected. Surgical approach leaves the hippocampal vascular perfusion intact until cold knife sections can be made across the hippocampal gyrus. Tissue is immediately fixed until cold knife sections can be made across the hippocampal gyrus. Tissue is immediately fixed for electron microscopy and golgi preparations in order to study neuronal patterns, dendritic arborization, spine types, distributions and numbers in the various subsections of the hippocampal and dentate cortices. Heretofore, virtually all thinking about epilepsy has centered on a single remote episode such as birth trauma, old anoxia or a scar which distorts the limbic cortex as the basis for the ictal activity. Our preliminary studies have shown degenerative lesions characteristic of early pathological alterations in neural tissues elsewhere and due to a variety of causes. Such changes as axonal degeneration, contraction of dendrites and development of varicosities on dendrites in patients with seizure histories of 10-20 years and no antecedent surgery forces one to seriously consider an active disease process. Thus, degeneration "hypersensitivity" may influence the ictal substrate in these cortices. We have outlined appropriate controls of both anatomical and technical factors in a modest program design for study of the human and primate hippocampus which will help us to draw certain conclusions about reasonable variations in this region's microstructural anatomy. These data will aid in our evaluation of an ongoing subtle, but destructive process which may continue through much of the childhood of the unfortunate patient with drug-resistant partial epilepsy. Our reseach group has had unusual success with this program of sophisticated diagnosis and therapy. The clinical results are reflected in data accumulated over the past ten years.